Author
Listed:
- Andrea Mencarelli
(Agency for Science, Technology and Research (A*STAR)
Duke−National University of Singapore Graduate Medical School)
- Hanif Javanmard Khameneh
(Agency for Science, Technology and Research (A*STAR))
- Jan Fric
(Agency for Science, Technology and Research (A*STAR)
St. Anne’s University Hospital)
- Maurizio Vacca
(Agency for Science, Technology and Research (A*STAR))
- Sary El Daker
(Institut Pasteur
Nelson R. Mandela Medical School)
- Baptiste Janela
(Agency for Science, Technology and Research (A*STAR))
- Jing Ping Tang
(Agency for Science, Technology and Research (A*STAR)
Cancer Science Institute of Singapore (CSI), National University of Singapore (NUS))
- Sabrina Nabti
(Agency for Science, Technology and Research (A*STAR))
- Akhila Balachander
(Agency for Science, Technology and Research (A*STAR))
- Tong Seng Lim
(Agency for Science, Technology and Research (A*STAR))
- Florent Ginhoux
(Agency for Science, Technology and Research (A*STAR))
- Paola Ricciardi-Castagnoli
(Agency for Science, Technology and Research (A*STAR)
Toscana Life Science Foundation)
- Alessandra Mortellaro
(Agency for Science, Technology and Research (A*STAR)
IRCCS San Raffaele Scientific Institute)
Abstract
The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11chighMHCII+ cells (Cnb1 CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3+ regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11chighMHCII+ cells to express IL-2. Deleting IL-2 in CD11chighMHCII+ cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin–NFAT–IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine.
Suggested Citation
Andrea Mencarelli & Hanif Javanmard Khameneh & Jan Fric & Maurizio Vacca & Sary El Daker & Baptiste Janela & Jing Ping Tang & Sabrina Nabti & Akhila Balachander & Tong Seng Lim & Florent Ginhoux & Pao, 2018.
"Calcineurin-mediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis,"
Nature Communications, Nature, vol. 9(1), pages 1-15, December.
Handle:
RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03495-3
DOI: 10.1038/s41467-018-03495-3
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